Escitalopram was approved for medical use in the United States in 2002.[2] In the United States the wholesale cost is about 2.04 USD per month as of 2017.[4] In the United Kingdom in 2015, escitalopram was more than 20 times as expensive as citalopram.[5] Escitalopram is sometimes replaced by twice the dose of citalopram.[5]

Escitalopram was approved by regulatory authorities for the treatment of major depressive disorder on the basis of four placebo controlled, double-blind trials, three of which demonstrated a statistical superiority over placebo.[6]

Controversy existed regarding the effectiveness of escitalopram compared to its predecessor citalopram. The importance of this issue followed from the greater cost of escitalopram relative to the generic mixture of isomers citalopram prior to the expiration of the escitalopram patent in 2012, which led to charges of evergreening. Accordingly, this issue has been examined in at least 10 different systematic reviews and meta analyses. The most recent of these have concluded (with caveats in some cases) that escitalopram is modestly superior to citalopram in efficacy and tolerability.[7][8][9][10]

In contrast to these findings, a 2011 review concluded that all second-generation antidepressants are equally effective, although may differ in onset and side effects.[11] Treatment guidelines issued by the National Institute of Health and Clinical Excellence and by the American Psychiatric Association generally reflect this viewpoint.[12][13]

In 2018, a systematic review and network meta-analysis comparing the efficacy and acceptability of 21 antidepressant drugs showed escitalopram to be one of the most effective antidepressants in head-to-head studies.[14]

An analysis conducted by the FDA found a statistically insignificant 1.5 to 2.4-fold (depending on the statistical technique used) increase of suicidality among the adults treated with escitalopram for psychiatric indications.[22][23][24] The authors of a related study note the general problem with statistical approaches: due to the rarity of suicidal events in clinical trials, it is hard to draw firm conclusions with a sample smaller than two million patients.[25]

Escitalopram is not associated with weight gain. For example, 0.6 kg mean weight change after 6 months of treatment with escitalopram for depression was insignificant and similar to that with placebo (0.2 kg).[26] 1.4–1.8 kg mean weight gain was reported in 8-month trials of escitalopram for depression,[27] and generalized anxiety disorder.[28] A 52-week trial of escitalopram for the long-term treatment of depression in elderly also found insignificant 0.6 kg mean weight gain.[29] Escitalopram may help reduce weight in those treated for binge eating associated obesity.[30]

Citalopram and escitalopram are associated with dose-dependent QT interval prolongation[31] and should not be used in those with congenital long QT syndrome or known pre-existing QT interval prolongation, or in combination with other medicines that prolong the QT interval. ECG measurements should be considered for patients with cardiac disease, and electrolyte disturbances should be corrected before starting treatment. In December 2011, the UK implemented new restrictions on the maximum daily doses.[32][33] The U.S. Food and Drug Administration and Health Canada did not similarly order restrictions on escitalopram dosage, only on its predecessor citalopram.[34]

Escitalopram should be taken with caution when using Saint John's wort.[35] Exposure to escitalopram is increased moderately, by about 50%, when it is taken with omeprazole. The authors of this study suggested that this increase is unlikely to be of clinical concern.[36] Caution should be used when taking cough medicine containing dextromethorphan (DXM) as serotonin syndrome, liver damage, and other negative side effects have been reported.

Some people experience persistent sexual side effects after they stop taking SSRIs.[39] This is known as post-SSRI sexual dysfunction (PSSD). Common symptoms include genital anesthesia, erectile dysfunction, anhedonia, decreased libido, premature ejaculation, vaginal lubrication issues, and nipple insensitivity in women. Rates are unknown, and there is no established treatment.[40]

Excessive doses of escitalopram usually cause relatively minor untoward effects such as agitation and tachycardia. However, dyskinesia, hypertonia, and clonus may occur in some cases. Plasma escitalopram concentrations are usually in a range of 20–80 μg/L in therapeutic situations and may reach 80–200 μg/L in the elderly, patients with hepatic dysfunction, those who are poor CYP2C19 metabolizers or following acute overdose. Monitoring of the drug in plasma or serum is generally accomplished using chromatographic methods. Chiral techniques are available to distinguish escitalopram from its racemate, citalopram.[42][43][44] Escitalopram seems to be less dangerous than citalopram in overdose and comparable to other SSRIs.[45]

Escitalopram increases intrasynaptic levels of the neurotransmitter serotonin by blocking the reuptake of the neurotransmitter into the presynaptic neuron. Of the SSRIs currently on the market, escitalopram has the highest selectivity for the serotonin transporter (SERT) compared to the norepinephrine transporter (NET), making the side-effect profile relatively mild in comparison to less-selective SSRIs.[47]

Escitalopram is a substrate of P-glycoprotein and hence P-glycoprotein inhibitors such as verapamil and quinidine may improve its blood-brain penetrability.[48] In a preclinical study in rats combining escitalopram with a P-glycoprotein inhibitor, its antidepressant-like effects were enhanced.[48]

Escitalopram, similarly to other SSRIs (with the exception of fluvoxamine), inhibits CYP2D6 and hence may increase plasma levels of a number of CYP2D6 substrates such as aripiprazole, risperidone, tramadol, codeine, etc. As much of the effect of codeine is attributable to its conversion (10%) to morphine its effectiveness will be reduced by this inhibition, not enhanced.[49] As escitalopram is only a weak inhibitor of CYP2D6, analgesia from tramadol may not be affected.[50] Escitalopram can also prolong the QT interval and hence it is not recommended in patients that are concurrently on other medications that have the ability to prolong the QT interval. Being a SSRI, escitalopram should not be given concurrently with MAOIs or other serotonergic medications.[47]

Escitalopram was developed in close cooperation between Lundbeck and Forest Laboratories. Its development was initiated in the summer of 1997, and the resulting new drug application was submitted to the U.S. FDA in March 2001. The short time (3.5 years) it took to develop escitalopram can be attributed to the previous extensive experience of Lundbeck and Forest with citalopram, which has similar pharmacology.[51] The FDA issued the approval of escitalopram for major depression in August 2002 and for generalized anxiety disorder in December 2003. On May 23, 2006, the FDA approved a generic version of escitalopram by Teva.[52] On July 14 of that year, however, the U.S. District Court of Delaware decided in favor of Lundbeck regarding the patent infringement dispute and ruled the patent on escitalopram valid.[53]

In 2006 Forest Laboratories was granted an 828-day (2 years and 3 months) extension on its US patent for escitalopram.[54] This pushed the patent expiration date from December 7, 2009 to September 14, 2011. Together with the 6-month pediatric exclusivity, the final expiration date was March 14, 2012.

In 2004, two separate civil suits alleging illegal marketing of citalopram and escitalopram for use by children and teenagers by Forest were initiated by two whistleblowers, one by a practicing physician named Joseph Piacentile, and the other by a Forest salesman named Christopher Gobble.[55] In February 2009, these two suits received support from the US Attorney for Massachusetts and were combined into one. Eleven states and the District of Columbia have also filed notices of intention to intervene as plaintiffs in the action. The suits allege that Forest illegally engaged in off-label promoting of Lexapro for use in children, that the company hid the results of a study showing lack of effectiveness in children, and that the company paid kickbacks to physicians to induce them to prescribe Lexapro to children. It was also alleged that the company conducted so-called "seeding studies" that were, in reality, marketing efforts to promote the drug's use by doctors.[56][57] Forest responded to these allegations that it "is committed to adhering to the highest ethical and legal standards, and off-label promotion and improper payments to medical providers have consistently been against Forest policy."[58] In 2010 Forest Pharmaceuticals Inc., agreed to pay more than $313 million to settle the charges over Lexapro and two other drugs, Levothroid and Celexa.[59]